Alkaptonuria and Homogentisic Acid Oxidase

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Questions and Answers

What is the worldwide prevalence of Alkaptonuria?

1 case in 1 000 000 births

1 case in 250 000 births (correct)

1 case in 500 000 births

1 case in 100 000 births

In which country is the prevalence of Alkaptonuria the highest?

India

Slovakia (correct)

The Dominican Republic

Jordan

How is the diagnosis of Alkaptonuria confirmed or excluded?

Blood test for phenylalanine and tyrosine levels

Physical examination for symptoms

Urine test for homogentisic acid using HPLC (correct)

Genetic testing for AKU mutations

What is the effect of nitisinone on Alkaptonuria treatment?

Inhibits the production of homogentisic acid Signup and view all the answers

What is the effect of ascorbic acid on homogentisic acid excretion?

Reduces the excretion of benzoquinone acetic acid Signup and view all the answers

What is the approximate number of identified AKU sufferers in 40 countries?

950 Signup and view all the answers

What is the recommended dietary restriction for Alkaptonuria treatment?

Restriction of phenylalanine and tyrosine Signup and view all the answers

What is the name of the enzyme inhibited by nitisinone?

4-hydroxyphenylpyruvate dioxygenase Signup and view all the answers

What causes the pigment to appear more rapidly in urine samples?

The addition of alkali to the urine Signup and view all the answers

What is the primary cause of Alkaptonuria?

Deficiency of homogentisic acid oxidase Signup and view all the answers

What is a common symptom of alkaptonuria in children and young adults?

No symptoms Signup and view all the answers

Where is homogentisic acid oxidase primarily found in mammalian systems?

Liver and kidney Signup and view all the answers

What is the term for the widespread deposition of pigment in alkaptonuria?

Ochronosis Signup and view all the answers

What is the ultimate product of the catabolism of homogentisic acid?

Fumaric acid and acetoacetic acid Signup and view all the answers

What is a common location for pigment deposition in alkaptonuria?

Both A and B Signup and view all the answers

How is Alkaptonuria inherited?

Autosomal recessive trait Signup and view all the answers

At what age do patients with alkaptonuria typically develop visible pigmentation?

After 30 years of age Signup and view all the answers

What is the prevalence of Alkaptonuria?

1 in 250,000 live births Signup and view all the answers

What is a common joint affected by alkaptonuria?

Both A and B Signup and view all the answers

What is a possible complication of alkaptonuria?

Kidney stones Signup and view all the answers

What happens to urine from patients with Alkaptonuria when exposed to air?

It darkens in color Signup and view all the answers

What is a possible outcome for older patients with alkaptonuria?

Becoming bedridden Signup and view all the answers

What is the name of the pigment formed from the accumulation of homogentisic acid and its oxidized derivative?

No specific name is mentioned in the content Signup and view all the answers

When do patients with Alkaptonuria usually excrete dark urine?

Several hours after urination Signup and view all the answers

Study Notes

Alkaptonuria (AKU)

Caused by a deficiency of homogentisic acid oxidase, leading to the accumulation of homogentisic acid (HGA)
HGA oxidase is found only in the liver and kidney, and plays a crucial role in the catabolism of phenylalanine and tyrosine

Etiology and Pathophysiology

Inherited as an autosomal recessive trait, with consanguinity noted by Garrod
A rare disorder affecting about 1 in 250,000 live births
Deficiency of homogentisate dioxygenase leads to the accumulation of HGA and its oxidized derivative, benzoquinone acetic acid
This can be polymerized to form a dark pigment, deposited in connective tissue

Clinical Abnormalities

Urine from AKU patients darkens when exposed to air, especially if alkalinized
Patients usually excrete acid urine of normal color, which turns dark on standing
Infants may be recognized due to their cloth diapers turning black or brown when washed with alkaline soap or detergent
Patients develop visible pigmentation (ochronosis) of the sclerae or cartilage of the ears after 30 years of age
Pigment may also be seen in the corneal, buccal mucosa, nails, and skin
Patients develop pain in weight-bearing joints, especially after 30 years of age
Joint-replacement surgery may be necessary at a relatively young age
Patients may become bedridden due to severe limitation of movement

Epidemiology

Worldwide prevalence of AKU is 1 case in 250,000 births
As of now, 950 AKU sufferers have been identified in 40 countries
More prevalent in Slovakia, the Dominican Republic, India, and Jordan
Highest prevalence is in Slovakia, where up to 1 in 19,000 are affected

Investigation and Diagnosis

Diagnosis can be confirmed or excluded by collecting urine for 24 hours and determining the amount of HGA using HPLC or specific enzymatic methods

Treatment and Outcomes

Recommended treatments include large doses of ascorbic acid (vitamin C) or dietary restriction of amino acids phenylalanine and tyrosine
Nitisinone may be effective in treating AKU, by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase and blocking the production of HGA
Low-dose nitisinone (2 mg/day) has been shown to reduce plasma and urine HGA by 95%

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Description

Learn about Alkaptonuria, a genetic disorder caused by the deficiency of homogentisic acid oxidase, leading to the accumulation of homogentisic acid. Understand the role of homogentisic acid oxidase in tyrosine metabolism and its impact on the body.